Reference - Detail
|Author||Wagatsuma A, Takayama Y, Hoshino T, Shiozuka M, Yamada S, Matsuda R, Mabuchi K.|
|Title||Pharmacological targeting of HSP90 with 17-AAG induces apoptosis of myogenic cells through activation of the intrinsic pathway.|
|Journal||Mol Cell Biochem|
We have shown that pharmacological inhibition of HSP90 ATPase activity induces apoptosis of myoblasts during their differentiation. However, the signaling pathways remain not fully characterized. We report that pharmacological targeting of HSP90 with 17-AAG activates the intrinsic pathway including caspase-dependent and caspase-independent pathways. 17-AAG induces the typical apoptotic phenotypes including PARP cleavage, chromatin condensation, and nuclear fragmentation with mitochondrial release of cytochrome c, Smac/DIABLO, procaspase-9 processing, and caspase-3 activation. AIF and EndoG redistribute from the mitochondria into the cytosol and are partially translocated to the nucleus in 17-AAG-treated cells. These results suggest that caspase-dependent and caspase-independent pathways should be considered in apoptosis of myogenic cells induced by inhibition of HSP90 ATPase activity.
|MeSH||Adenosine Triphosphatases / antagonists & inhibitors* Animals Apoptosis / drug effects* Apoptosis Inducing Factor / metabolism Apoptosis Regulatory Proteins Benzoquinones / pharmacology* Blotting, Western Caspase 3 / metabolism Caspase 9 / metabolism Cell Nucleus / drug effects Chromatin / metabolism Cytochromes c / metabolism Endodeoxyribonucleases / metabolism Enzyme Activation HSP70 Heat-Shock Proteins / metabolism HSP90 Heat-Shock Proteins / antagonists & inhibitors* Intracellular Signaling Peptides and Proteins / metabolism Lactams, Macrocyclic / pharmacology* Mice Mitochondria / drug effects Mitochondria / enzymology Mitochondria / metabolism Mitochondrial Proteins / metabolism Myoblasts / cytology Myoblasts / drug effects* Poly(ADP-ribose) Polymerases / metabolism Proteolysis Proto-Oncogene Proteins c-akt / antagonists & inhibitors X-Linked Inhibitor of Apoptosis Protein / metabolism|
|Human and Animal Cells||C2C12(RCB0987)|